Slides
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1 Topline Results of the RINGSIDE Phase 3 Study of Varegacestat in Desmoid Tumors Investor Webcast Dec 15, 2025
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2 Forward Looking Statements Disclosures For purposes of this notice, the “presentation” that follows shall mean and include the slides that follow, any oral presentation of the slides by members of management of Immunome, Inc. (“Immunome”) or any person on its behalf, any question-and- answer session that follows that oral presentation, hard copies of this document and any materials distributed at, or in connection with, that presentation. References to “we,” “our,” and “us” refers to Immunome and its subsidiaries. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any Immunome securities. Forward-Looking Statements Statements in this presentation that are not purely historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. We use words such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “vision,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “promising,” “projected,” “first step,” “ongoing,” or the negative of these terms, and similar words or expressions to identify these forward- looking statements. These forward-looking statements include statements regarding: Immunome’s regulatory and development timeline for its pipeline assets, including filing an NDA for varegacestat, submitting INDs for its preclinical assets, and commencing and completing clinical trials, receiving and reporting data from such clinical trials for its IND and clinical stage assets, and other anticipated milestones; the best-in-class potential of varegacestat and its ability to become the new standard of care for treating desmoid tumors; Immunome’s plans to deliver best-in-class commercial execution through its commercial readiness, hiring, market access and market shaping plans; the anticipation that varegacestat, if approved, will have >90% payer coverage; Immunome’s expectation to provide a best-in-class patient treatment envelope and its ability to drive compliance and starts; the potential of Immunome’s targeted oncology therapies to provide long term value creation; and other statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future. These forward-looking statements are based on Immunome’s current expectations and involve assumptions that may never materialize or may prove to be incorrect; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors: the RINGSIDE topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data and such topline data may not accurately reflect the complete results of the trial; the risk that our NDA submission for varegacestat is delayed based on regulatory feedback or otherwise, and that regulatory approvals for Immunome’s programs and product candidates are not obtained, are delayed or are subject to unanticipated conditions, including the risk that the results of our trials for varegacestat may not be deemed sufficient by the FDA to serve as the basis for an NDA submission or regulatory approval of varegacestat; the risks associated with the potential safety and other complications from varegacestat; the labelling for varegacestat, if approved; the scope, progress and expansion of developing and commercializing varegacestat, if approved; the size and growth of the market for varegacestat and the rate and degree of market acceptance thereof; the risk that Immunome will not be able to realize the benefits of its strategic transactions; uncertainties related to Immunome’s capital requirements and Immunome’s expected cash runway; Immunome’s ability to grow and advance its pipeline and successfully execute on its business plan; and other risks and uncertainties included under the caption “Risk Factors” in Immunome’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, filed with the Securities and Exchange Commission (“SEC”) on November 6, 2025. These documents can also be accessed on Immunome’s website at www.immunome.com by clicking on the link “Financials” under the “Investors” tab. Except as required by law, Immunome assumes no obligation and does not intend to update any forward- looking statements included in this presentation. Product Candidates In this presentation, we may discuss current and potential future product candidates that have not yet undergone clinical trials or been approved for marketing by the U.S. Food and Drug Administration or other governmental authority. No representation is made as to the safety or effectiveness of these current or potential future product candidates for the use for which such product candidates are being studied. Industry and Market Data In this presentation, we rely on and refer to publicly available information and statistics regarding market participants in the sectors in which we compete and other industry data. Any comparison of us to the industry or to any of our competitors is based on this publicly available information and statistics and such comparisons assume the reliability of the information available to us. We obtained this information and statistics from third-party sources, including reports by market research firms and company filings. While we believe such third-party information is reliable, there can be no assurance as to the accuracy or completeness of the indicated information. We have not independently verified the information provided by the third-party sources. Trademarks This presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this presentation may be listed without the TM, SM © or ® symbols, but we will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these trademarks, service marks, trade names and copyrights.
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AGENDA Opening Remarks Clay Siegall, PhD RINGSIDE Topline Results Bob Lechleider, MD Treatment Landscape Mrinal Gounder, MD Memorial Sloan Kettering Cancer Center Commercialization Roee Shahar Next Steps & Close Clay Siegall, PhD
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Clay Siegall, PhD President and CEO
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Generally well-tolerated with manageable safety profile Confirmed Objective Response Rate2: 56% Progression-Free Survival1: Hazard Ratio 0.16 (p<0.0001) Median Best Tumor Volume Reduction3: 83% (1) Primary endpoint (2) Key secondary endpoint (3) Exploratory endpoint 2Q26 NDA Submission Planned Varegacestat Demonstrated Exceptional Results For Patients Study Met Primary and All Key Secondary Endpoints
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Bob Lechleider, MD Chief Medical Officer
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Varegacestat is a Gamma Secretase Inhibitor with a Differentiated Pharmacokinetic Profile Desmoid tumors are driven by nuclear accumulation of β-CATENIN resulting from cross-talk between WNT and NOTCH pathways2 Kasper et al. Sources: (1) Figure adapted from Kasper et al., ESMO 2022. Abstr LBA2, based on Andersson et al., Development, 2011 and Bui and Kummar, Oncotarget, 2017; (2) Federman, NPJ Precision Oncology, 2022; (3) Immunome data on file; (4) Aung et al., Investigational New Drugs. 2018; (5) Varegacestat Investigator’s Brochure Version 8.0 78% Longer Half-Life than Nirogacestat3 Sustained Exposure Above Target Threshold4,5 1.2 mg Once Daily 7
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Key Inclusion Criteria • Progressed within last 12 months1 • Treatment naïve or recurrent/refractory disease appropriate for systemic treatment RINGSIDE is the Largest Phase 3 Study in Desmoid Tumors Design consistent with prior registrational trials Key Endpoints • Primary: Progression-free survival2 (PFS) • Alpha-controlled key secondary • Objective Response Rate • Tumor Volume3 at Week 24 • Worst Pain Intensity at Week 124 • Safety and tolerability • Additional efficacy assessments, including median best percent change in Tumor Volume3 (1) Progression was defined as ≥20% increase per RECIST v1.1 (2) PFS was defined as time from randomization until the date of assessment of radiographic progression as assessed Blinded Independent Central Review (BICR) based on RECIST v1.1 (3) Measured by T2 weighted MRI or CT per BICR (4) Measured using Desmoid Tumor Symptom Scale Item 1 from the GOunder/Desmoid Tumor Research Foundation Desmoid Tumor Symptom/Impact Scale (GODDESS) Global Phase 3 Double-Blind Placebo-Controlled R Varegacestat 1.2mg QD, n=79 Placebo, n=77 Varegacestat 1.2mg QD Open Label Extension Cross over to OLE if progressive disease Cross over to OLE if active at primary analysis 1:1 8
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Varegacestat Achieved Primary Endpoint 84% Reduction in the Risk of Progression or Death vs Placebo Progression-Free Survival: HR 0.16; 95% CI: 0.071, 0.375; p < 0.0001
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Par 56% ORR With Varegacestat vs 9% With Placebo (p<0.0001) -83% Median Best Percent Change in Tumor Volume With Varegacestat vs +11% With Placebo -83% Best Percent Change in Tumor Size with Varegacestat PR Varegacestat Demonstrates Robust Antitumor Activity PD 10
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• Varegacestat was generally well-tolerated, with a manageable safety profile consistent with the GSI class of medicines • The most common adverse events for participants in the treatment arm were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%) and cough (34%) • Most events were grade 1 or 2 • 55.6% of premenopausal women experienced ovarian toxicity • There were no deaths on study Varegacestat was Generally Well-tolerated with a Manageable Safety Profile 11
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• Thank you to the patients and investigators in the RINGSIDE study • New Drug Application expected for varegacestat during 2Q 2026 • Presentation of full data from RINGSIDE Phase 3 anticipated at an upcoming medical conference • Additional clinical trials planned Next Steps
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Mrinal Gounder, MD Sarcoma Medical Oncologist Drug Development Specialist Memorial Sloan Kettering Cancer Center
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• Desmoid tumors often strike in young adulthood, with 1,000-1,650 patients diagnosed each year in the US1 • Can lead to debilitating pain, deformity, and life-threatening organ damage depending on location1 • Quality of life is a major challenge with a majority of patients experiencing chronic pain that can significantly limit physical functioning1 • Up to ~60-80% of patients experience recurrence, which can be exacerbated by surgery1 • Following progression during initial active surveillance, systemic therapy is recommended for ~75% of tumors based on location2,3 Approved systemic therapy options remain limited with only one approved therapy Desmoid Tumors are Locally Aggressive & Debilitating Sources: (1) Bektas et al., Advances in Therapy, 2023; (2) The Desmoid Tumor Working Group, European Journal of Cancer, 2020; (3) The Desmoid Tumor Working Group, JAMA Oncology, 2024 14
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Unmet Need Remains for Effective, FDA-approved Therapies Suitable for Chronic Nature of Desmoid Tumors 1) Bektas M, Bell T, Khan S, et al. Desmoid tumors: A comprehensive review. Adv Ther.2023;40(9):3697-3722. doi:10.1007/s12325-023-02592-0 2) Bektas M, Bell T, Khan S, et al. Desmoid tumors: A comprehensive review. Adv Ther.2023;40(9):3697-3722. doi:10.1007/s12325-023-02592-0; 3) Colombo C, Miceli R, Le Péchoux C, et al. Sporadic extra abdominal wall desmoid-type fibromatosis:Surgical resection can be safely limited to a minority of patients. Eur J Cancer. 2015;51(2):186-192.doi:10.1016/j.ejca.2014.11.019; 4) Easter DW, Halasz NA. Recent trends in the management of desmoid tumors. Summary of 19 cases and review of the literature. Ann Surg. 1989;210(6):765-769. 5) Skubitz KM. Biology and treatment of aggressive fibromatosis or desmoid tumor. Mayo Clin Proc. 2017;92(6):947-964 6) NCT02066181 7) DeFi (NCT03785964) Treatment & Management of Desmoid Tumors Local Treatment Why We Need More Treatment Options Spontaneous regression is not common1,2,3,6,7 Tumor location limits feasibility; Up to 77% recurrence rate after Surgery4,5 Historically modest response rates range from ~30-40%.6,7 Active Surveillance SYSTEMIC THERAPY TKI GSI Chemo Systemic Therapy
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Elevating an Established Class and Solidifying the Role of GSIs in Desmoid Tumor Treatment ORR (%) 2018 2023 2025 ORR: 41% ORR: 56% Placebo ORR: 8% Placebo ORR: 20% ORR: 33% Sorafenib 400mg Once Daily Oral NCT02066181; N=87 Nirogacestat 150 mg Twice-Daily Oral DeFi; n=142 Varegacestat 1.2mg Once-Daily Oral RINGSIDE; N=156 TKI Era GSI Era Phase 3 Studies in Desmoid Tumors Reliance on limited P1/2 and observational studies and local therapy FOR ILLUSTRATIVE PURPOSES ONLY: no head-to-head clinical trial has been conducted evaluating varegacestat against nirogacestat or other candidates or products. Differences exist between trial designs and subject characteristics, and strong caution should be exercised when comparing data across unrelated studies. Placebo ORR: 9% Pre-2018
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Patient Case: A Decade of Disease, a Dramatic Reduction in Tumor Volume Within Months Surgery Hydroxy Urea Sorafenib Imatinib Treated in RINGSIDE (part A) 1.2mg (‘21-24) Patient History • Diagnosed in 2010 • A 25 Y/O male patient, with a pelvic and left leg desmoid tumor • No history of FAP (Familial Adenomatous Polyposis) 2010 2011 2012 2021 BASELINE: October 2021 Vol: 22.93 cm3 FOLLOW-UP 1: March 2022 Vol. 7.54 cm3 FOLLOW-UP 2: June 2022 Vol. 2.83cm3 Response & Tumor Volume Reduction
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Data Support Potential For Varegacestat to Become SOC in the Treatment of Desmoid Tumors RINGSIDE is the largest randomized Phase 3 trial in desmoid tumors • PFS, ORR, Tumor Volume reduction are best in class Progression-free survival hazard ratio of 0.16 is striking Safety profile is manageable and consistent with the GSI class 18
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Roee Shahar EVP - Commercial
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Launch Strategy Become Standard of Care treatment of Desmoid Tumors START Drive patient initiation on varegacestat SUPPORT Sustained benefit and adherence with a once-daily treatment SCALE Efficiently expand reach across the community through treatment center growth GSI Non-GSI Treatment 10-11k Actively Managed Patients (US) 1 ~85 Sarcoma Centers-of-Excellence4 ~50% of patients have desmoid tumors for more than 5 years 2 A Long, Chronic, Treatment Journey 1) Immunome Analysis 2) K Mercier et al. ESMO Sarcoma 2024 Poster 3) Immunome Primary Market Research 4) Immunome Analysis Dx. Rx Rx Patients may receive ~1.5–2 years of treatment, pause, and return for treatment3
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Differentiated Clinical Profile and Commercial Execution Expected to Support Rapid Adoption 2026 Commercial Readiness • Distribution & supply chain leverages prior oncology launches • Manufacturing capacity sufficient for a blockbuster • Launch preparation anchored to priority review Market Shaping • KOL familiarity expected to accelerate uptake • Patient treatment envelope expected to drive increased compliance and starts • KOLs and advocacy engaged – building anticipation Team • Commercial hires have demonstrated success in oncology launches • Highly experienced commercial and medical teams Market Access • US & EMA orphan designation has favorable pricing implications • Launch focused on 85 sarcoma centers of excellence expected to drive efficiency and quick uptake • >90% anticipated payer coverage Launch 21
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Patient Support is Key for the Success of Varegacestat “The promising results with varegacestat from the RINGSIDE trial drive forward the shared mission of finding effective, safe therapies and ultimately a cure for every person living with a desmoid tumor." Lynne Hernandez & Katie Doyle Myers – Executive Directors of DTRF 22
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Clay Siegall, PhD President and CEO
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Varegacestat NDA Submission Planned 2Q26 IM-1021 Ph1 Data 2026 Novel solid-tumor targeted ADCs ROR1 ADC Gamma Secretase Inhibitor Positive RINGSIDE Phase 3 topline data IM-1617 IND 2026 IM-1340 IND 2026 IM-1335 IND 2026 ADC portfolio including the HC74 platform represents substantial value Varegacestat at approval provides strong first product Proven, successful leadership Multiple programs expected to enter clinic in 2026 IM-3050 Ph1 Initiation Early 2026 FAP RLT Accelerating the Pursuit of Breakthrough Oncology Therapies Anticipated Milestones